Trogocytosis of peptide-MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils

Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1111-1116. doi: 10.1073/pnas.1615973114. Epub 2017 Jan 17.

Abstract

Th2 immunity plays important roles in both protective and allergic responses. Nevertheless, the nature of antigen-presenting cells responsible for Th2 cell differentiation remains ill-defined compared with the nature of the cells responsible for Th1 and Th17 cell differentiation. Basophils have attracted attention as a producer of Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) expression and function as antigen-presenting cells are matters of considerable controversy. Here we revisited the MHC-II expression on basophils and explored its functional relevance in Th2 cell differentiation. Basophils generated in vitro from bone marrow cells in culture with IL-3 plus GM-CSF displayed MHC-II on the cell surface, whereas those generated in culture with IL-3 alone did not. Of note, these MHC-II-expressing basophils showed little or no transcription of the corresponding MHC-II gene. The GM-CSF addition to culture expanded dendritic cells (DCs) other than basophils. Coculture of basophils and DCs revealed that basophils acquired peptide-MHC-II complexes from DCs via cell contact-dependent trogocytosis. The acquired complexes, together with CD86, enabled basophils to stimulate peptide-specific T cells, leading to their proliferation and IL-4 production, indicating that basophils can function as antigen-presenting cells for Th2 cell differentiation. Transfer of MHC-II from DCs to basophils was also detected in draining lymph nodes of mice with atopic dermatitis-like skin inflammation. Thus, the present study defined the mechanism by which basophils display MHC-II on the cell surface and appears to reconcile some discrepancies observed in previous studies.

Keywords: MHC class II; basophil; dendritic cell; trogocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / immunology*
  • Antigen-Presenting Cells / immunology*
  • Basophils / immunology*
  • Calcitriol / analogs & derivatives
  • Calcitriol / toxicity
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / pharmacology
  • Dendritic Cells / immunology*
  • Dermatitis, Contact / immunology
  • Dermatitis, Contact / pathology
  • Genes, MHC Class II / drug effects
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Immunological Synapses / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments / immunology
  • Specific Pathogen-Free Organisms
  • Th2 Cells / immunology
  • Tryptases / genetics

Substances

  • Cytokines
  • Histocompatibility Antigens Class II
  • I-A(b) antigen, mouse
  • I-E-antigen
  • Peptide Fragments
  • calcipotriene
  • Mcpt8 protein, mouse
  • Tryptases
  • Calcitriol